4-[(2-Methoxyethoxy)methoxy]aniline → 5-fluoro-N2-(4-((2-methoxyethoxy)methoxy)phenyl)-N4-(3-nitrophenyl)pyrimidine-2,4-diamine

HRID 1482664Notes

Reaction equation

HRID 1482664 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[C:5]([F:18])=[CH:4][N:3]=1.[CH3:19][O:20][CH2:21][CH2:22][O:23][CH2:24][O:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1.CCCCCC.C(OCC)(=O)C>C(O)C.C(O)(=O)C>[F:18][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)=[N:7][C:2]([NH:30][C:29]2[CH:31]=[CH:32][C:26]([O:25][CH2:24][O:23][CH2:22][CH2:21][O:20][CH3:19])=[CH:27][CH:28]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 131356894-[(2-Methoxyethoxy)methoxy]anilineHCID 21226206Ethyl acetate hexaneHCID 591746392-chloro-5-fluoro-N-(3-nitrophenyl)pyrimidin-4-amine

Product 1

HCID 867243285-fluoro-N2-(4-((2-methoxyethoxy)methoxy)phenyl)-N4-(3-nitrophenyl)pyrimidine-2,4-diamineYield 62.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 702EthanolSolvent2×

Procedure

To a solution of 2-chloro-5-fluoro-N-(3-nitrophenyl)pyrimidin-4-amine (0.400 g) and 4-[(2-methoxyethoxy)methoxy]aniline (0.458 g), in ethanol (20 mL), was added acetic acid (4.65 mg). The reaction mixture was heated to reflux for 24 hr. Completion of reaction was monitored by TLC using hexane:ethyl acetate (8:2) as mobile phase. After completion of the reaction, ethanol was removed under reduced pressure at 40° C. To the residue water (25 mL) was added and mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and distilled under reduced pressure to give 0.4 g of 5-fluoro-N2-(4-((2-methoxyethoxy)methoxy)phenyl)-N4-(3-nitrophenyl)pyrimidine-2,4-diamine as a solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 24 hr
  3. customCompletion of reaction
  4. customwas removed under reduced pressure at 40° C
  5. additionTo the residue water (25 mL) was added
  6. extractionmixture was extracted with ethyl acetate
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. distillationdistilled under reduced pressure

Sources & evidence

ORD record
ord-6bb8a3d3904c461f9e923e561de26218
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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